Discovery of a dual-action compound for metallo-β-lactamase inhibition and biofilm clearance to reverse CRE resistance

IF 3.2 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry Pub Date : 2025-08-11 DOI:10.1016/j.jinorgbio.2025.113028

Mingjun Liu , Chen Wu , Xuanliang Zhang , Yushi Wang , Yuxuan Wei , Yuzhou Hu , Zouyi Sun , Cheng Chen , Youzhen Ma

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Abstract

The emergence of carbapenem-resistant Enterobacteriaceae (CRE) poses a severe threat to global public health due to its multidrug resistance and limited treatment options. In this study, QA, a zinc ion chelator with potent inhibitory activity against metallo-β-lactamases (MBLs), was identified through high-throughput screening and biochemical analysis. QA effectively inhibits MBLs by chelating zinc ions and demonstrates potent biofilm clearance capabilities, ultimately reversing carbapenem-resistant Enterobacteriaceae (CRE) resistance. Synergistic antibacterial effects were observed when QA was combined with meropenem and other β-lactam antibiotics, significantly enhancing their efficacy. These findings highlight the dual-action potential of QA as a zinc ion chelator and biofilm disruptor, offering a promising strategy for combating CRE infections and multidrug-resistant bacteria.

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发现具有金属β-内酰胺酶抑制和生物膜清除双重作用的化合物以逆转CRE耐药性

耐碳青霉烯肠杆菌科（CRE）的出现，由于其多药耐药和有限的治疗选择，对全球公共卫生构成严重威胁。本研究通过高通量筛选和生化分析，鉴定出一种对金属β-内酰胺酶（MBLs）具有较强抑制活性的锌离子螯合剂QA。QA通过螯合锌离子有效抑制MBLs，并显示出强大的生物膜清除能力，最终逆转碳青霉烯抗性肠杆菌科（CRE）耐药性。与美罗培南及其他β-内酰胺类抗菌药物联合应用，抗菌效果明显增强。这些发现突出了QA作为锌离子螯合剂和生物膜破坏者的双重作用潜力，为对抗CRE感染和多重耐药细菌提供了一种有希望的策略。

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来源期刊

Journal of Inorganic Biochemistry 生物-生化与分子生物学

CiteScore

7.00

自引率

10.30%

发文量

336

审稿时长

41 days

期刊介绍： The Journal of Inorganic Biochemistry is an established international forum for research in all aspects of Biological Inorganic Chemistry. Original papers of a high scientific level are published in the form of Articles (full length papers), Short Communications, Focused Reviews and Bioinorganic Methods. Topics include: the chemistry, structure and function of metalloenzymes; the interaction of inorganic ions and molecules with proteins and nucleic acids; the synthesis and properties of coordination complexes of biological interest including both structural and functional model systems; the function of metal- containing systems in the regulation of gene expression; the role of metals in medicine; the application of spectroscopic methods to determine the structure of metallobiomolecules; the preparation and characterization of metal-based biomaterials; and related systems. The emphasis of the Journal is on the structure and mechanism of action of metallobiomolecules.